Separating agent for optical isomer

ABSTRACT

Provided is a complex obtained by reacting a polymer compound derivative obtained by modifying part of hydroxy groups or amino groups of a polymer compound having the hydroxy groups or amino groups with a compound represented by the following general formula (I) with one or more kinds of compounds represented by the following general formulae (II) to (V): (I) A-X—Si(Y) n R 3-n  (where A, X, Y, R, and n are as defined in claim  1 ) ; (II) M(OR 1 ) n R 2   4-n ; (III) Al(OR 1 ) p R 2   3-p ; (IV) Mg(OR 1 ) g R 2   2-q  (where M, R 1 , R 2 , n, p, and q are as defined in claim  1 ); and (V) (where R 3 , R 4 , R 5 , and R 6  are as defined in claim  1 ).

TECHNICAL FIELD

The present invention relates to a complex used in a separating agentfor optical isomers.

BACKGROUND ART

It has recently become more and more important to obtain large amountsof optical isomers in a short time period with ease in terms of theresearch and development of drugs and high-performance materials.

Optical resolution by chromatography has conventionally been attractingattention remarkably in various fields including analytical chemistry,organic chemistry, medicine, and pharmacy, and a large number of chiralstationary phases have been reported in the world. In particular, forexample, an ester derivative or carbamate derivative obtained bychemically modifying a polysaccharide such as cellulose or amylose as anoptically active polymer serves as a chiral stationary phase having ahigh optical resolution, and a filler for chromatography using suchderivative has been known to the public. A filler for chromatographyusing such polymer compound derivative is used in a state of beingcarried by a carrier such as silica gel for the purposes of, forexample, increasing the ratio at which a column is filled with thefiller, and improving the ease of handling and mechanical strength ofthe filler.

For example, Patent Document 1 describes a filler for chromatographyobtained by causing a carrier such as silica to carry a cellulosederivative containing an aromatic ring. In addition, Patent Document 2describes a filler for chromatography obtained by causing a carrier suchas silica to carry an alkyl-substituted phenylcarbamate derivative of apolysaccharide in which 80 to 100% of the hydroxy groups thereof aresubstituted. Further, Patent Document 3 describes a separating adsorbentobtained by causing a carrier formed of porous silica gel to carry anoptically active polymer.

However, the above conventional filler for chromatography using apolymer compound such as a polysaccharide derivative has the followingconstitution: mainly an inorganic carrier is caused to carry the polymercompound derivative on itself by physical adsorption. Such filler forchromatography involves the following constraint: a solvent thatdissolves the polymer compound such as a polysaccharide derivativecannot be used as a mobile phase. In addition, it is difficult toseparate large amounts of optical isomers in one stroke with the fillerbecause only the molecules of the polymer compound present at thesurface on the inorganic carrier contribute to optical resolution.

In order that the filler may serve as a separating agent for opticalisomers suitable for fractionating large amounts of optical isomers inone stroke, for example, attempts have been made to increase the amountof the polymer compound derivative having an ability to separate opticalisomers carried by the inorganic carrier, and a separating agent inwhich such attempts are made has been developed (see, for example,Patent Document 4).

However, the amount of the polymer compound derivative which theinorganic carrier can carry on itself is limited, and there has beenroom for further development of a separating agent optimum for theseparation of large amounts of optical isomers.

Meanwhile, separating agents for optical isomers each using no inorganiccarrier and each formed only of a polymer compound derivative have alsobeen developed (see, for example, Patent Documents 5 and 6). Any suchseparating agent allows one to separate larger amounts of opticalisomers in one stroke than those in the case of such filler as describedabove because the separating agent is formed only of a portion thatcontributes to the separation of the optical isomers.

However, any such separating agent for optical isomers has a lowmechanical strength, and its use under high pressures at high flow ratesis restricted because the separating agent is formed only of an organiccompound. In addition, the following problem arises: a solvent usedcannot be changed during the analysis of the optical isomers because theorganic compound swells and contracts.

-   Patent Document 1: JP 60-142930 A-   Patent Document 2: JP 8-13844 B-   Patent Document 3: JP 6-91956 B-   Patent Document 4: WO 2002/030853 A1-   Patent Document 5: JP 3181349 B-   Patent Document 6: WO 2004/086029 A1

DISCLOSURE OF THE INVENTION Problems to be Solved by the Invention

The present invention provides a complex for use in the production of aseparating agent for optical isomers having the followingcharacteristics: a ratio of the molecules of a polymer compoundderivative that contribute to the separation of optical isomers in theseparating agent for optical isomers is made larger than a conventionalone, and the separating agent has a high mechanical strength.

Means for Solving the Problems

The present invention has been made in view of the above circumstances,and the inventors of the present invention have developed a complex thatcan be used in a separating agent for optical isomers as a result oftheir extensive studies. The inventors have found that: since thecomplex includes a structure in which an element such as silicon and apolymer compound derivative are three-dimensionally crosslinked asdescribed later, a solvent to be used is not limited, and the complexcan not only be excellent in solvent resistance but also show anincreased ratio of the molecules of the polymer compound derivative thatcontribute to the separation of optical isomers; and, when the complexis used in a separating agent for optical isomers, the separating agentshows an increased mechanical strength.

In the present invention, a complex obtained by the following procedureis used in the separation of optical isomers: a polymer compoundderivative obtained by modifying part of the hydroxy or amino groups ofa polymer compound having the hydroxy or amino groups and a specificcompound to be described later are caused to react with each other. Tobe additionally specific, the present invention provides a complexobtained by causing a polymer compound derivative obtained by modifyingpart of the hydroxy or amino groups of the above polymer compound havingthe hydroxy or amino groups with a compound represented by the followinggeneral formula (I) and one or more kinds of compounds represented bythe following general formulae (II) to (V) to react with each other:

[Chem 1]

A-X—Si(Y)_(n)R_(3-n)   (I)

where A represents a reactive group which reacts with a hydroxy or aminogroup, X represents an alkylene group which has 1 to 18 carbon atoms andwhich may have a branch, or an arylene group which may have asubstituent, Y represents a reactive group which reacts with a silanolgroup to form a siloxane bond, R represents an alkyl group which has 1to 18 carbon atoms and which may have a branch, or an aryl group whichmay have a substituent, and n represents an integer of 1 to 3;

[Chem 2]

M(OR¹)_(n)R² _(4-n)   (II)

[Chem 3]

Al(OR¹)_(p)R² _(3-p)   (III)

[Chem 4]

Mg(OR¹)_(q)R² _(2-q)   (IV)

where M represents silicon (Si), titanium (Ti), zirconium (Zr), orchromium (Cr), Al represents aluminum, Mg represents magnesium, R¹represents hydrogen or an alkyl group having 1 to 12 carbon atoms, R²represents an alkyl group which has 1 to 18 carbon atoms and which mayhave a branch or an aryl group which may have a substituent, nrepresents an integer of 1 to 4, p represents an integer of 1 to 3, andq represents an integer of 1 or 2;

[Chem 5]

[Si(OR³)_(n)R⁴ _(3-n)]-—(X)—[Si(OR⁵)_(n)R⁶ _(3-n)]  (V)

where R³, R⁴, R⁵, and R⁶ each independently represent an alkyl groupwhich has 1 to 18 carbon atoms and which may have a branch or an arylgroup which may have a substituent, and X represents an alkylene groupwhich has 1 to 18 carbon atoms and which may have a branch or an arylenegroup which may have a substituent.

In addition, the present invention provides a complex obtained by thefollowing procedure, the complex being in a bead form: a polymercompound derivative obtained by modifying part of the hydroxy or aminogroups of a polymer compound having the hydroxy or amino groups with acompound represented by the above general formula (I) and one or morekinds of compounds represented by the above general formulae (II) to (V)are caused to react with each other.

In addition, the present invention provides a method of producing acomplex, the method including the steps of: dissolving a polymercompound derivative obtained by modifying part of the hydroxy or aminogroups of a polymer compound having the hydroxy or amino groups with acompound represented by the above general formula (I) and one or morekinds of compounds represented by the above general formulae (II) to (V)in an organic solvent to prepare a solution; and dropping the solutioninto an aqueous solution of a surfactant or a proton-donating solventwhile stirring the aqueous solution or the solvent.

Further, the present invention provides a separating agent for opticalisomers, the separating agent containing a complex obtained by thefollowing procedure: a polymer compound derivative obtained by modifyingpart of the hydroxy or amino groups of a polymer compound having thehydroxy or amino groups with a compound represented by the above generalformula (I) and one or more kinds of compounds represented by the abovegeneral formulae (II) to (V) are caused to react with each other.

Effect of the Invention

The complex according to the present invention obtained by the followingprocedure is extremely useful as a high-performance material, and iseffectively used particularly in the production of a separating agentfor use in the separation of optical isomers: a polymer compoundderivative modified with a compound represented by the above generalformula (I) and one or more kinds of compounds represented by the abovegeneral formulae (II) to (V) are caused to react with each other.

When the complex of the present invention is used in a separating agentfor use in the separation of optical isomers, the separating agent canseparate large amounts of the optical isomers in one stroke because aratio of the molecules of the polymer compound derivative thatcontribute to the separation of the optical isomers in the complex islarge.

In addition, when the complex of the present invention is used in aseparating agent for use in the separation of optical isomers, theseparating agent shows a high mechanical strength because the complexcontains a three-dimensionally crosslinked inorganic substance.

In addition, the polymer compound derivative and the three-dimensionallycrosslinked inorganic substance are chemically bonded to each other inthe complex of the present invention, so even a solvent that maydissolve the polymer compound derivative can be used, and the complex isexcellent in solvent resistance.

In addition, when the complex of the present invention is used in aseparating agent for use in the separation of optical isomers, theswelling and contraction of the separating agent are suppressed, and theseparating agent is suitable not only for the analysis of the opticalisomers but also for an application where the optical isomers areseparated because the complex contains a compound having a functionalgroup that reacts with an alkoxysilyl group.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a view illustrating the structure of a polymer compoundderivative (cellulose derivative) obtained in each of Examples 1 to 3,5, and 9.

FIG. 2 shows secondary electron images (photographs)) of beads obtainedin examples photographed with a scanning electron microscope.

FIG. 3 shows secondary electron images (photographs)) of beads of anexample before and after use in SFC photographed with a scanningelectron microscope.

FIG. 4 is a view illustrating the structural formulae of compoundsoptically separated in examples and comparative examples in which thenumerical values described below the structural formulae correspond tothe numerical values representing the kinds of racemic bodies describedin Table 1.

FIG. 5 is a view illustrating the results of the optical resolution ofthe molecules of warfarin (11) with a column obtained in Example 1.

FIG. 6 is a view illustrating the ¹H NMR spectrum of a cellulose3,5-dimethylphenylcarbamate containing alkoxysilyl groups (derivative-A)at 80° C. in DMSO-d₆ obtained in Example 1.

FIG. 7 is a view illustrating the ¹H NMR spectrum of a cellulose3,5-dimethylphenylcarbamate containing alkoxysilyl groups (derivative-B)at 80° C. in DMSO-d₆ obtained in Example 2.

FIG. 8 is a view illustrating the ¹H NMR spectrum of a cellulose3,5-dimethylphenylcarbamate containing alkoxysilyl groups (derivative-C)at 80° C. in DMSO-d₆ obtained in Example 3.

FIG. 9 is a view illustrating the structure of a polymer compoundderivative (amylose derivative) obtained in Example 7.

BEST MODE FOR CARRYING OUT THE INVENTION

<1> Polymer Compound Derivative for Use in Production of Complex of thePresent Invention

The polymer compound derivative to be used in the present invention isformed by modifying part of the hydroxy or amino groups of a polymercompound having the hydroxy or amino groups with molecules of a compoundrepresented by the following general formula (I):

[Chem 6]

A-X—Si(Y)_(n)R_(3-n)   (I)

where A represents a reactive group which reacts with a hydroxy or aminogroup, X represents an alkylene group which has 1 to 18 carbon atoms andwhich may have a branch, or an arylene group which may have asubstituent, Y represents a reactive group which reacts with a silanolgroup to form a siloxane bond, R represents an alkyl group which has 1to 18 carbon atoms and which may have a branch, or an aryl group whichmay have a substituent, and n represents an integer of 1 to 3.

The above-mentioned polymer compound to be used in the production of thepolymer compound derivative used in the present invention is preferablyan optically active organic polymer compound, or more preferably apolysaccharide. Any one of the natural polysaccharides, syntheticpolysaccharides, and natural product-denatured polysaccharides can bepreferably used as the polysaccharide to be used in the presentinvention as long as the polysaccharide to be used has chirality. Ofthose, a polysaccharide in which monosaccharides are regularly bonded toeach other is suitable because the polysaccharide can additionallyimprove the ability of a filler containing the polymer compoundderivative to separate optical isomers.

Specific examples of the polysaccharide include 3-1,4-glucan(cellulose), α-1,4-glucan (amylose, amylopectin), α-1,6-glucan(dextran), β-1,6-glucan (pustulan), β-1,3-glucan (curdlan,schizophyllan), α-1,3-glucan, β-1,2-glucan (Crown Gall polysaccharide),β-1,4-galactan, β-1,4-mannan, α-1,6-mannan, β-1,2-fructan (inulin),β-2,6-fructan (levan), β-1,4-xylan, β-1,3-xylan, β-1,4-chitosan,β-1,4-N-acetylchitosan (chitin), pullulan, agarose, alginic acid,α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin. Starch containingamylose is also included.

Of those, preferred are cellulose, amylose, β-1,4-chitosan, chitin,β-1,4-mannan, β-1,4-xylan, inulin, curdlan, and the like, with whichhigh-purity polysaccharides can be easily obtained, and cellulose andamylose are more preferred.

The polysaccharide has a number average degree of polymerization(average number of pyranose or furanose rings in one molecule) ofpreferably 5 or more, or more preferably 10 or more, and there is noparticular upper limit for the number average degree of polymerization;the number average degree of polymerization is preferably 1,000 or lessin terms of the ease of handling of the polysaccharide, and is morepreferably 5 to 1,000, still more preferably 10 to 1,000, orparticularly preferably 10 to 500.

In the present invention, the polymer compound derivative means apolymer compound obtained by modifying part of the hydroxy or aminogroups of a polymer compound having the hydroxy or amino groups. Whenthe polymer compound to be used as a raw material for the production ofthe polymer compound derivative is a polysaccharide, the above-mentionedpolymer compound derivative is a polysaccharide derivative.

In the above general formula (I):

A represents a reactive group that reacts with a hydroxy or amino group,and the reactive group is preferably, for example, a chlorocarbonylgroup, a carboxyl group, an isocyanate group, a glycidyl group, or athiocyanate group;

X represents an alkylene group which has 1 to 18 carbon atoms and whichmay have a branch or may have a heteroatom introduced into itself, or anarylene group which may have a substituent, examples of the substituentwhich the arylene group may have include an alkyl group having 1 to 12carbon atoms, an alkoxy group having 1 to 12 carbon atoms, an alkylthiogroup having 1 to 12 carbon atoms, a cyano group, a halogen, an acylgroup having 1 to 8 carbon atoms, an acyloxy group having 1 to 8 carbonatoms, a hydroxy group, an alkoxycarbonyl group having 1 to 12 carbonatoms, a nitro group, an amino group, and a dialkylamino group havingalkyl groups each having 1 to 8 carbon atoms, specific preferableexamples of X include alkylene groups each of which has 1 to 18 carbonatoms and each of which may have a branch, and out of the examples, anethylene group, a propylene group, a butylene group, or the like isparticularly preferable;

Y represents a reactive group that reacts with a silanol group to form asiloxane bond, and the reactive group is preferably, for example, analkoxy group having 1 to 12 carbon atoms or a halogen, or particularlypreferably, for example, a methoxy group, an ethoxy group, or a propoxygroup;

R represents an alkyl group which has 1 to 18 carbon atoms and which mayhave a branch or an aryl group which may have a substituent, andexamples of the substituent which the aryl group may have include analkyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12carbon atoms, an alkylthio group having 1 to 12 carbon atoms, a cyanogroup, a halogen, an acyl group having 1 to 8 carbon atoms, an acyloxygroup having 1 to 8 carbon atoms, a hydroxy group, an alkoxycarbonylgroup having 1 to 12 carbon atoms, a nitro group, an amino group, and adialkylamino group having alkyl groups each having 1 to 8 carbon atoms;and

n represents an integer of 1 to 3.

Examples of the compound represented by the above-mentioned generalformula (I) include 3-isocyanatepropyltriethoxysilane,3-isocyanatepropyltrimethoxysilane,3-isocyanatepropyldiethoxymethylsilane,2-isocyanateethyltriethoxysilane, 4-isocyanatephenyltriethoxysilane,3-glycidoxypropyltrimethoxysilane, 3-glycidoxypropyltriethoxysilane, and3-thiocyanatepropyltriethoxysilane. Preferred are3-isocyanatepropyltriethoxysilane and3-isocyanatepropyltrimethoxysilane.

In the above-mentioned polymer compound derivative, molecules of thecompound represented by the above-mentioned general formula (I) areintroduced into part of the hydroxy or amino groups of theabove-mentioned polymer compound having the hydroxy or amino groups.

The positions at which the molecules of the compound represented by theabove-mentioned general formula (I) are introduced into the hydroxy oramino groups of the above-mentioned polymer compound having the hydroxyor amino groups are not particularly limited.

In addition, the above-mentioned term “part” can be represented as aratio of introduction of the molecules of the compound represented bythe above-mentioned general formula (I) into the hydroxy or amino groupsof the polymer compound having the hydroxy or amino groups. The ratio ofintroduction is preferably 1.0 to 35%, more preferably 1.5 to 20%, orparticularly preferably 2.0 to 10%. The reason why a ratio ofintroduction of the molecules of the compound represented by theabove-mentioned general formula (I) of less than 1.0% or in excess of35% is not preferable is as follows: when the ratio is less than 1.0%,the yield in which each of the polymer compound derivative and a beadcomposed of the polymer compound derivative is produced reduces while,when the ratio exceeds 35%, the optical separation ability of a fillercontaining the polymer compound derivative reduces.

In addition, the above-mentioned ratio of introduction (%) is defined asfollows: when the polymer compound to be used in the production of theabove-mentioned polymer compound derivative of the present invention hasonly hydroxy groups, the ratio of introduction is a numerical valueobtained by multiplying a ratio of the number of hydroxy groups modifiedwith the molecules of the compound represented by the above-mentionedgeneral formula (I) to the total number of the hydroxy groups of thepolymer compound by 100; when the above-mentioned polymer compound hasonly amino groups, the ratio of introduction is a numerical valueobtained by multiplying a ratio of the number of amino groups modifiedwith the molecules of the compound represented by the above-mentionedgeneral formula (I) to the total number of the amino groups by 100; orwhen the above-mentioned polymer compound has hydroxy groups and aminogroups, the ratio of introduction is a numerical value obtained bymultiplying a ratio of the sum of the numbers of hydroxy groups andamino groups modified with the molecules of the compound with which thehydroxy or amino groups are modified to the sum of the total number ofthe hydroxy groups and the total number of the amino groups by 100. Inaddition, in the present invention, the same definition as thatdescribed above is applicable also to the ratio of introduction ofmolecules of a compound except the compound represented by theabove-mentioned general formula (I).

In the above-mentioned polymer compound derivative, at least part of thehydroxy or amino groups except the hydroxy or amino groups modified withthe molecules of the compound represented by the above-mentioned generalformula (I) are preferably further modified with molecules of a compoundhaving a functional group which acts on an optical isomer.

The above-mentioned functional group is a functional group, which actson an optical isomer in a sample containing optical isomers to beseparated. The action of the functional group on the optical isomercannot be uniquely defined because the kind of the functional groupvaries depending on the kinds of the optical isomers to be separated;the action is not particularly limited as long as the action sufficesfor the optical resolution of the above-mentioned optical isomers withthe above-mentioned polymer compound derivative. Examples of theabove-mentioned functional group include a group containing an aromaticgroup, which may have a substituent, and an aliphatic group having acyclic structure. The above-mentioned aromatic group can contain aheterocyclic ring or a condensed ring. Examples of the substituent,which the above-mentioned aromatic group may have, include an alkylgroup having up to about 8 carbon atoms, a halogen, an amino group, andan alkoxyl group. The above-mentioned functional group is selected inaccordance with the kinds of the above-mentioned optical isomers to beseparated.

In addition, the molecules of the compound having the functional groupwhich acts on an optical isomer are preferably introduced into the atleast part of the hydroxy or amino groups except the hydroxy or aminogroups modified with the molecules of the compound represented by theabove-mentioned general formula (I) through a urethane bond, an esterbond, or an ether bond for a hydroxy group and a urea bond or an amidebond for an amino group; a urethane bond and a urea bond areparticularly preferable for a hydroxy group and an amino group,respectively. Therefore, the above-mentioned compound having thefunctional group, which acts on an optical isomer, is a compound havinga functional group, which can react with a hydroxy or amino group of theabove-mentioned polymer compound as well. The above-mentioned compoundhaving a functional group which can react with a hydroxy or amino groupmay be any compound as long as the compound is an isocyanic acidderivative, a carboxylic acid, an acid halide, an alcohol, or any othercompound having reactivity with a hydroxy or amino group.

It should be noted that neither the ratio of introduction of themolecules of the compound having the above-mentioned functional groupnor the positions at which the molecules of the compound are introducedin the polymer compound is particularly limited, and the ratio and thepositions are appropriately selected in accordance with, for example,the kind of the functional group and the kind of the polymer compound.

The above-mentioned compound having a functional group which acts on anoptical isomer is particularly preferably a compound containing anatomic group represented by the following general formula (VI) or (VII):

[Chem 7]

—CO—R′  (VI)

—CO—NH—R′  (VII)

where R′ represents an aliphatic or aromatic hydrocarbon group which maycontain a heteroatom, and the aliphatic or aromatic hydrocarbon groupmay be unsubstituted or may be substituted with one or more groupsselected from the group consisting of a hydrocarbon group which has 1 to12 carbon atoms and which may contain a heteroatom, a cyano group, ahalogen, a hydroxy group, a nitro group, an amino group, and adialkylamino group containing two alkyl groups each having 1 to 8 carbonatoms.

Examples of the monovalent aromatic hydrocarbon group represented by R′described above include a phenyl, naphthyl, phenanthryl, anthracyl,indenyl, indanyl, furyl, thionyl, pyryl, benzofuryl, benzthionyl, indyl,pyridyl, pyrimidyl, quinolinyl, and isoquinolinyl group. In addition,examples of the substituent for the monovalent aromatic hydrocarbongroup represented by R′ include alkyl groups each having 1 to 12 carbonatoms, alkoxy groups each having 1 to 12 carbon atoms, alkylthio groupseach having 1 to 12 carbon atoms, a cyano group, halogens, acyl groupseach having 1 to 8 carbon atoms, acyloxy groups each having 1 to 8carbon atoms, a hydroxy group, alkoxycarbonyl groups each having 1 to 12carbon atoms, a nitro group, amino groups, and a dialkylamino groupcontaining two alkyl groups each having 1 to 8 carbon atoms. Inaddition, as the aliphatic hydrocarbon group represented by R′ describedabove, desired is an alicyclic compound containing more than 3 rings, ormore preferably more than 5 rings, or an alicyclic compound having across linked structure. Of those, preferred is a cyclohexyl,cyclopentyl, norbornyl, cycloadamantyl pentyl group, or the like.

In the present invention, part of the hydroxy or amino groups except thehydroxy or amino groups modified with the molecules of the compoundrepresented by the above-mentioned general formula (I) is preferablymodified with molecules of one or more kinds of compounds selected fromthe group consisting of phenyl isocyanate, tolyl isocyanate,naphthylethyl isocyanate, 3,5-dimethylphenyl isocyanate,3,5-dichlorophenyl isocyanate, 4-chlorophenyl isocyanate,3,5-dinitrophenyl isocyanate, 1-phenylethyl isocyanate, benzoic acid orbenzoic acid halide, and 4-methylphenyl carboxylic acid (halide). Thosegroups are particularly preferably modified with molecules of3,5-dimethylphenyl isocyanate.

In the polymer compound derivative of the present invention, the sum ofthe ratio of introduction of the molecules of the compound representedby the above-mentioned general formula (I) and the ratio of introductionof the molecules of the compound having the above-mentioned functionalgroup is preferably 90 to 100%, more preferably 97 to 100%, orparticularly preferably 100%.

<2> Method of Producing Polymer Compound Derivative of the PresentInvention

The polymer compound derivative used for producing the complex of thepresent invention can be produced as described below. That is, a firstmethod of producing the polymer compound derivative of the presentinvention includes at least:

a first modifying step of modifying part of the hydroxy or amino groupsof a polymer compound having the hydroxy or amino groups, the polymercompound being dissolved, with molecules of a compound except a compoundrepresented by the above-mentioned general formula (I); and

a second modifying step of modifying hydroxy or amino groups of theabove-mentioned polymer compound which are not modified with themolecules of the compound except the compound represented by theabove-mentioned general formula (I) in the above-mentioned firstmodifying step with molecules of the compound represented by theabove-mentioned general formula (I).

The above-mentioned first modifying step is preferably performed beforethe above-mentioned second modifying step in order that the compoundrepresented by the above-mentioned general formula (I) may beefficiently and controllably introduced into the above-mentioned polymercompound.

It should be noted that the above-mentioned production method mayfurther include a step of dissolving the polymer compound in order thata dissolved polymer compound having hydroxy or amino groups may beobtained. In the above-mentioned dissolving step, a known method can beemployed for dissolving the polymer compound; when the polymer compoundto be dissolved is hardly soluble in a solvent or the like, the methodpreferably includes a step of swelling the polymer compound. Inaddition, when a dissolved polymer compound having hydroxy or aminogroups is commercially available, the dissolved polymer compound may bepurchased and used.

As a solvent which swells the polymer compound (such as polysaccharide)in the above-mentioned swelling step, an amide-based solvent ispreferably used. Examples of the solvent include a mixed solution suchas a mixed solution of N,N-dimethyl aceteamide and lithium chloride,N-methyl-2-pyrrolidone and lithium chloride, or1,3-dimethyl-2-imidazolidinone and lithium chloride. A mixture solutionof N,N-dimethyl aceteamide and lithium chloride is particularlypreferably used.

The above-mentioned dissolving step is preferably performed under anitrogen atmosphere. In addition, when the above-mentioned polymercompound is a polysaccharide, the polysaccharide is dissolved under, forexample, conditions including a temperature of 20 to 100° C. and a timeperiod of 1 to 24 hours; one skilled in the art can appropriately adjustthe conditions depending on the polymer compound to be used.

The above-mentioned first modifying step is a step of modifying part ofthe hydroxy or amino groups of the polymer compound having the hydroxyor amino groups, the polymer compound being dissolved, with molecules ofa compound having at least a functional group which acts on an opticalisomer and a functional group which can react with a hydroxy or aminogroup. A known method can be employed in the modification. The hydroxyor amino groups of the polymer compound are particularly preferablymodified with the molecules of the compound having a functional groupwhich acts on an optical isomer in an amount corresponding to 60 to 100mol % of the hydroxy or amino groups of the polymer compound in a mixedsolution of dimethylacetamide, lithium chloride, and pyridine at 80 to100° C. for 1 to 24 hours under a nitrogen atmosphere in order that theratio of introduction of the molecules of the compound having thefunctional group may be controlled. In particular, the reactiontemperature, the reaction time, and the additive amount of the compoundhaving a functional group which acts on an optical isomer, each plays animportant role in adjusting the ratio of introduction of the moleculesof the compound having the above-mentioned functional group.

It should be noted that the positions at which the molecules of thecompound having at least a functional group which acts on an opticalisomer and a functional group which can react with a hydroxy or aminogroup are introduced in the polymer compound derivative in the presentinvention are not particularly limited.

The above-mentioned second modifying step is a step of modifying thehydroxy or amino groups of the polymer compound the hydroxy or aminogroups of which are not completely modified with the molecules of thecompound having at least a functional group which acts on an opticalisomer and a functional group which can react with a hydroxy or aminogroup in the above-mentioned first modifying step with the molecules ofthe compound represented by the above-mentioned general formula (I). Aknown method can be employed in the modification. The hydroxy or aminogroups before modification of the polymer compound are particularlypreferably modified with the molecules of the compound represented bythe above-mentioned general formula (I) in an amount corresponding to 1to 10 mol % of the hydroxy or amino groups before modification of thepolymer compound in a mixed solvent of dimethylacetamide, lithiumchloride, and pyridine at 80 to 100° C. for 1 to 24 hours under anitrogen atmosphere in order that the ratio of introduction of themolecules of the compound represented by the above-mentioned generalformula (I) may be controlled. Of those conditions, the additive amountof the compound represented by the above-mentioned general formula (I)plays a particularly important role in controlling the ratio ofintroduction of the molecules of the compound represented by theabove-mentioned general formula (I).

It should be noted that the positions at which the molecules of thecompound represented by the above-mentioned general formula (I) areintroduced in the polymer compound derivative in the present inventionare not particularly limited. When unreacted hydroxy or amino groups arepresent at the time of the completion of the above-mentioned secondmodifying step, they are caused to react with the molecules of thecompound having the functional groups used in the first modifying step.

In addition, a method of producing the polymer compound derivative to beused in the present invention may be a method including at least: aprotective group-introducing step of introducing a protective group intoeach of part of the hydroxy or amino groups of the polymer compoundhaving the hydroxy or amino groups, the polymer compound beingdissolved; a first modifying step of modifying the hydroxy or aminogroups remaining in the polymer compound into which the protective grouphas been introduced with molecules of a compound except the compoundrepresented by the above-mentioned general formula (I); an eliminatingstep of eliminating the introduced protective group to regeneratehydroxy groups; and a second modifying step of modifying the regeneratedhydroxy groups or the amino groups with the molecules of the compoundrepresented by the above-mentioned general formula (I). In theabove-mentioned production method including the protectivegroup-introducing step and the eliminating step, the hydroxy or aminogroups at specific positions of the polymer compound can be modifiedwith the molecules of the compound represented by the above-mentionedgeneral formula (I).

In the above-mentioned production method including the protectivegroup-introducing step and the eliminating step, the protective group tobe introduced in the protective group-introducing step is notparticularly limited as long as the group can be eliminated from ahydroxy or amino group more easily than a compound with which a hydroxyor amino group is modified in each modifying step is. A compound forintroducing the protective group can be determined on the basis of thereactivity of a hydroxy or amino group to be protected or modified andthe reactivity of the compound with a hydroxy or amino group. Thecompound is, for example, a compound having a triphenylmethyl group(trityl group), a diphenylmethyl group, a tosyl group, a mesyl group, atrimethylsilyl group, or a dimethyl(t-butyl)silyl group, and a compoundhaving a trityl group or a trimethylsilyl group is suitably used.

The introduction of the protective group into a hydroxy or amino group,and the modification of a hydroxy or amino group with a modifyingcompound can each be performed by a known proper reaction in accordancewith the kind of a compound to be caused to react with a hydroxy oramino group. In addition, the elimination of the protective group from ahydroxy or amino group in the eliminating step can be performed by aknown method such as hydrolysis with an acid or alkali without anyparticular limitation.

According to the above-mentioned first production method, there is noneed to take the trouble to introduce a protective group, so the numberof steps can be reduced. As a result, a reduction in cost for theproduction of the polymer compound derivative can be achieved. Inaddition, according to the above-mentioned second production step, amolecule of the compound represented by the above-mentioned generalformula (I) can be introduced into a hydroxy group at a predeterminedposition of the polymer compound with reliability.

It should be noted that the employment of the above-mentioned firstproduction method of the present invention allows a predetermined amountof the hydroxy or amino groups of the polymer compound derivative notmodified with the molecules of the compound except the compoundrepresented by the above-mentioned general formula (I) in the firstmodifying step to be modified with the molecules of the compoundrepresented by the above-mentioned general formula (I) in the secondmodifying step. Therefore, the ratio of introduction of the molecules ofthe compound represented by the above-mentioned formula (I) into thepolymer compound having hydroxy or amino groups can be controlled byadjusting the amount of the compound represented by the above-mentionedgeneral formula (I) in the second modifying step.

When the ratio of introduction of the molecules of the compoundrepresented by the above-mentioned general formula (I) in the polymercompound derivative of the present invention is determined, each of thefollowing two methods each involving the use of ¹H NMR is preferablyemployed. When a reaction between the compound represented by theabove-mentioned general formula (I) and a hydroxy or amino group iscomplete, the ratios of introduction of the molecules of the compoundrepresented by the above-mentioned general formula (I) determined by therespective methods show an identical value. In the present invention,the following method (2) was employed.

(1) The ratio of introduction of the molecules of a compound except thecompound represented by the above-mentioned general formula (I) in thepolymer compound derivative is determined from a result of elementalanalysis for the polymer compound derivative before the introduction ofthe compound represented by the above-mentioned general formula (I).After that, the ratio of introduction of silyl groups in the polymercompound derivative into which the compound represented by theabove-mentioned general formula (I) has been introduced is calculatedfrom a ratio of the polymer compound derivative between a proton of afunctional group of the compound except the compound represented by theabove-mentioned general formula (I) and a proton of a functional groupdirectly bonded to silicon of the compound represented by theabove-mentioned general formula (I), and the calculated value is definedas the ratio of introduction of the molecules of the compoundrepresented by the above-mentioned general formula (I) in the polymercompound derivative.(2) After the completion of the modifying steps, a ratio between aproton of a functional group of the compound except the compoundrepresented by the above-mentioned general formula (I) and a proton of afunctional group directly bonded to silicon of the compound representedby the above-mentioned general formula (I) is determined on theassumption that the hydroxy or amino groups of the polymer compoundderivative of the present invention are completely modified withmodifying groups. Then, the ratio of introduction of the molecules ofthe compound represented by the above-mentioned general formula (I) inthe polymer compound derivative is calculated.

<3>

(1) Compounds Represented by General Formulae (II) to (IV)

Compounds represented by the following general formulae (II) to (IV)used in the present invention are not particularly limited as long aseach of the compounds can react with the group Y of the compoundrepresented by the above general formula (I), and can be used in theproduction of the complex of the present invention:

[Chem 8]

M(OR¹)_(n)R² _(4-n)   (II)

[Chem 9]

Al(OR¹)_(p)R² _(3-p)   (III)

[Chem 10]

Mg(OR¹)_(q)R² _(2-q)   (IV)

where M represents silicon (Si), titanium (Ti), zirconium (Zr), orchromium (Cr), Al represents aluminum, Mg represents magnesium, R¹represents hydrogen or an alkyl group having 1 to 12 carbon atoms, R²represents an alkyl group which has 1 to 18 carbon atoms and which mayhave a branch or an aryl group which may have a substituent, nrepresents an integer of 1 to 4, p represents an integer of 1 to 3, andq represents an integer of 1 or 2.

One kind of the compounds represented by the above general formulae (II)to (IV) may be used alone, or two or more kinds of them may be used incombination; one or more kinds of compounds represented by the abovegeneral formula (II) are preferably used.

In the above general formula (II), M preferably represents silicon (Si),R¹ preferably represents an alkyl group having 1 to 6 carbon atoms,examples of the substituent which the aryl group represented by R² mayhave include an alkyl group having 1 to 12 carbon atoms, an alkoxy grouphaving 1 to 12 carbon atoms, an alkylthio group having 1 to 12 carbonatoms, a cyano group, a halogen, an acyl group having 1 to 8 carbonatoms, an acyloxy group having 1 to 8 carbon atoms, a hydroxy group, analkoxycarbonyl group having 1 to 12 carbon atoms, a nitro group, anamino group, and a dialkylamino group having alkyl groups each having 1to 8 carbon atoms, R² preferably represents a methyl group or a phenylgroup, and n preferably represents 3 or 4.

Specific examples of the compound represented in the above generalformula (II) include tetraethoxysilane, tetramethoxysilane,tetra-n-propoxysilane, tetraisopropoxysilane, tetra-n-butoxysilane,tetraisobutoxysilane, tetra-sec-butoxysilane, tetra-t-butoxysilane,tetrapentyloxysilane, tetrahexyloxysilane, triethoxymethylsilane, andtriethoxyphenylsilane. Of those, tetraethoxysilane is particularlypreferable.

The amount of the compounds represented by the above general formulae(II) to (IV) used at the time of the production of the complex of thepresent invention can be appropriately adjusted so that the content oforganic substances in the complex may be a suitable one as describedlater.

(2) Compounds Represented by General Formula (V)

Compounds represented by the following general formula (V) used in thepresent invention are not particularly limited as long as each of thecompounds can react with the group Y of the compound represented by theabove general formula (I), and can be used in the production of thecomplex of the present invention:

[Chem 11]

[Si(OR³)_(n)R⁴ _(3-n)]—(X)—[Si(OR⁵)_(n)R⁶ _(3-n)]  (V)

where R³, R⁴, R⁵, and R⁶ each independently represent an alkyl groupwhich has 1 to 18 carbon atoms and which may have a branch or an arylgroup which may have a substituent, and X represents an alkylene groupwhich has 1 to 18 carbon atoms and which may have a branch or an arylenegroup which may have a substituent.

Examples of the substituents which the above aryl group represented byany one of R³, R⁴, R⁵, and R⁶, and the above alkylene or arylene grouprepresented by X may have include an alkyl group having 1 to 12 carbonatoms, an alkoxy group having 1 to 12 carbon atoms, an alkylthio grouphaving 1 to 12 carbon atoms, a cyano group, a halogen, an acyl grouphaving 1 to 8 carbon atoms, an acyloxy group having 1 to 8 carbon atoms,a hydroxy group, an alkoxycarbonyl group having 1 to 12 carbon atoms, anitro group, an amino group, and a dialkylamino group having alkylgroups each having 1 to 8 carbon atoms.

Specific examples of the compound represented by the above generalformula (V) include bis(trimethoxysilyl)methane,bis(triethoxysilyl)methane, 1,1-bis(trimethoxysilyl)ethane,1,1-bis(triethoxysilyl)ethane, 1,2-bis(trimethoxysilyl)ethane,1,3-bis(trimethoxysilyl)propane, 1,3-(triethoxysilyl)propane,2,2-bis(trimethoxysilyl)propane, 2,2-bis(triethoxysilyl)propane,1,4-bis(trimethoxysilyl)benzene, 1,4-bis(triethoxysilyl)benzene, and1,2-bistriethoxysilylethane. Of which, 1,2-bistriethoxysilylethane isparticularly preferable.

One kind of the compounds represented by the above general formula (V)may be used alone, or two or more kinds of them may be used incombination.

The amount of the compounds represented by the above general formula (V)used at the time of the production of the complex of the presentinvention can be appropriately adjusted so that the content of theorganic substances in the complex may be a suitable one as describedlater.

In the production of the complex of the present invention to bedescribed later, one kind of the compounds represented by any one of theabove general formulae (II) to (V) may be used alone, or two or morekinds of them may be used in combination. A particularly preferablecombination is, for example, as follows: one or more kinds of thecompounds represented by the above general formulae (II) to (IV) and oneor more kinds of the compounds represented by the above general formula(V) are combined with each other. When one or more kinds of thecompounds represented by the above general formulae (II) to (IV) and oneor more kinds of the compounds represented by the above general formula(V) are used in combination in the production of the complex of thepresent invention, the one or more kinds of the compounds represented bythe above general formulae (II) to (IV) and the one or more kinds of thecompounds represented by the above general formula (V) are combined at amolar ratio “former:latter” of preferably 0.1 to 10:1, or particularlypreferably 0.2 to 5:1.

The total amount of the one or more kinds of the compounds representedby the above general formulae (II) to (IV) and the one or more kinds ofthe compounds represented by the above general formula (V) when thesecompounds are used in combination can be appropriately adjusted so thatthe content of the organic substances in the complex may be a suitableone as described later.

<4> Complex of the Present Invention

The complex of the present invention is obtained by causing the abovepolymer compound derivative and one or more kinds of compoundsrepresented by the above general formulae (II) to (V) to react with eachother. The content of the above polymer compound derivative in thecomplex of the present invention is preferably 10 to 90 wt %, morepreferably 20 to 80 wt %, or particularly preferably 30 to 70 wt % withrespect to the total amount of the complex from the viewpoint of anability to separate optical isomers.

Here, as described below, the content of the above polymer compoundderivative in the complex of the present invention can be estimated byusing a value for the content of the organic substances of the complexdetermined from the following weight: a weight reduction when thecomplex is heated to 800° C. by thermogravimetric analysis is consideredto be the weight of the organic substances. To be specific, the content(wt %) of the polymer compound derivative in the complex of the presentinvention can be determined by using the following equation. It shouldbe noted that, when the compound represented by the above generalformula (II) is used alone, the content of the polymer compoundderivative in the complex of the present invention is calculated inconsideration of the content (wt %) of an organic substance derived fromthe compound represented by the above general formula (II) used in thepresent invention as represented by the following equation (see Example4 below).

[Eq. 1]

Content (wt %) of polymer compound derivative=A−B(100−A)/(100−B)

“A” described above represents the content (wt %) of the organicsubstances in the complex, and “B” described above represents thecontent (wt %) of the organic substance derived from the compoundrepresented by the above general formula (II) used in the production ofthe complex.

In addition, when the compound represented by the above general formula(V) is used alone, the content of the polymer compound derivative in thecomplex of the present invention is calculated in consideration of thecontent (wt %) of an organic substance derived from the compoundrepresented by the above general formula (V) calculated by employing thesame method as that described in Example 4 below as represented by thefollowing equation.

[Eq. 2]

Content (wt %) of polymer compound derivative=A−C(100−A)/(100−C)

“A” described above represents the content (wt %) of the organicsubstances in the complex, and “C” described above represents thecontent (wt %) of the organic substance derived from the compoundrepresented by the above general formula (V) used in the production ofthe complex.

In addition, for example, when one kind of the compounds represented bythe above general formula (II) and one kind of the compounds representedby the above general formula (V) are used in combination, the content ofthe polymer compound derivative in the complex of the present inventionis calculated in consideration of the content (wt %) of an organicsubstance derived from each of the compound represented by the abovegeneral formula (II) and the compound represented by the above generalformula (V) described above as represented by the following equation.

[Eq. 3]

Content (wt %) of polymer compoundderivative=A−{B[a/(a+b)]+C[b/(a+b)]}(100−A)/[100−{B[a/(a+b)]+C[b/(a+b)}]

“A” described above represents the content (wt %) of the organicsubstances in the complex, “B” described above represents the content(wt %) of the organic substance derived from the compound represented bythe above general formula (II) used in the production of the complex,“C” described above represents the content (wt %) of the organicsubstance derived from the compound represented by the above generalformula (V) used in the production of the complex, and “a” and “b”represent the molar ratios of the compound represented by the abovegeneral formula (II) and the compound represented by the above generalformula (V) mixed at the time of the production of the complex,respectively.

It should be noted that, even when two or more kinds of the compoundsrepresented by the above general formulae (II) to (IV) and two or morekinds of the compounds represented by the above general formula (V) areused, the content of the organic substances in the complex can becalculated by the same calculation method as that described above withthe contents of the organic substances derived from the respectivecompounds similarly calculated and the molar ratios of the respectivecompounds.

The complex of the present invention may be in, for example, apulverized form; to be specific, as described later, the complex ispreferably turned into beads. When the complex of the present inventionis in a bead form, the beads can be used as they are in a separatingagent for optical isomers. The term “complex” as used in the presentinvention refers to a complex obtained by causing the above polymercompound derivative and one or more kinds of the compounds representedby the above general formulae (II) to (V) to react with each other asdescribed above. At the time of the formation of the complex, the groupY introduced into the above polymer compound derivative and the one ormore kinds of the compounds represented by the above general formulae(II) to (V) react with each other. As a result of the reaction, part ofthe molecules of the one or more kinds of the compounds represented bythe above general formulae (II) to (V) and part of the molecules of theabove polymer compound derivative are bonded to each other, andfurthermore, the molecules of the one or more kinds of the compoundsrepresented by the above general formulae (II) to (V) are bonded to eachother. Thus, a repeating unit of an M-O bond (where M represents any oneof the same elements as those appearing in the description of the abovegeneral formula (II) and O represents oxygen), a repeating unit of anAl—O bond, a repeating unit of an Mg—O bond, and/or Si—X—Si—O (where Xrepresents any one of the same groups as those appearing in thedescription of the above general formula (V)) are/is formed in thecomplex, so the complex may have a structure in which the polymercompound derivative and any such repeating unit are three-dimensionallycrosslinked.

The complex of the present invention can be produced by, for example,mixing the above polymer compound derivative and one or more kinds ofthe compounds represented by the above general formulae (II) to (V) withan acid in advance to crosslink them partially and dropping theresultant into an aqueous solution of a surfactant.

It should be noted that an anionic surfactant or a cationic surfactantcan be used as the above surfactant in the invention of the subjectapplication. When the anionic surfactant out of those surfactants isused, the surfactant is added to water so that the concentration of thesurfactant in the above aqueous solution of the surfactant may bepreferably 0.02 to 2 wt %, or particularly preferably 0.04 to 1 wt %;similarly, when the cationic surfactant is used, the surfactant is addedto water so that the concentration may be preferably 0.02 to 2 wt %, orparticularly preferably 0.04 to 1 wt %.

Examples of the anionic surfactants may include sodiumdodecylbenzenesulfonate, sodium alkyl naphthalene sulfonate, sodiumaryl-alkyl-polyethersulfonate, sodium3,3-disulfonediphenylurea-4,4-diazo-bis-amino-8-naphthol-6-sulfonate,ortho-carboxybenzene-azo-dimethylaniline, sodium2,2,5,5-tetramethyl-triphenylmethane-4,4-diazo-bis-β-naphthol-6-sulfonate,sodium dialkylsulfosuccinate, sodium dodecylsulfate, sodiumtetradecylsulfate, sodium pentadecylsulfate, sodium octylsulfate, sodiumoleate, sodium dodecanate, sodium caprate, sodium caprylate, sodiumcaproate, potassium stearate, and calcium oleate. Of those, sodiumdodecylsulfate is preferably used.

Examples of the cationic surfactants may include alkylbenzenedimethylammonium chloride, alkyltrimethyl ammonium chloride, and distearylammonium chloride. Of those, alkyltrimethyl ammonium chloride having analkyl group with 12 to 18 carbon atoms is preferably used.

<5> Beads of the Present Invention

The present invention provides beads as one specific form of the complexobtained by causing the above polymer compound derivative and one ormore kinds of the compounds represented by the above general formulae(II) to (V) to react with each other. The beads in the present inventionare nearly spherical particles or spherical particles, and their shapeshave the following characteristic: when the longest diameter andshortest diameter of each of, for example, about twenty particles aremeasured, the average longest diameter-to-shortest diameter ratio of theparticles is 1.0 to 5.0, preferably 1.0 to 2.0, or more preferably 1.0to 1.3. In the present invention, the particle shapes and particle sizesof the beads can be determined from an image photographed with, forexample, a scanning electron microscope (SEM).

It should be noted that hereinafter, the beads obtained in the inventionof the subject application are also referred to as “hybrid beads”.

The above-mentioned beads according to the present invention areobtained by a method involving: gradually adding a polymer compoundderivative such as a polysaccharide derivative modified with thecompound represented by the above-mentioned general formula (I), thepolymer compound derivative being dissolved in an organic solvent, to anaqueous solution of a surfactant or a solvent containing aproton-donating solvent such as methanol, the aqueous solution or thesolvent being sufficiently stirred, to prompt a crosslinking reactionbetween the molecules of the polymer compound derivative with at leastone of the compounds represented by the above-mentioned general formulae(II) to (V); and isolating an insoluble portion. The organic solvent tobe used here may be any solvent as long as the polymer compoundderivative such as a polysaccharide derivative and at least one of thecompounds represented by the above-mentioned general formulae (II) to(V) are soluble therein; the solvent is particularly preferablyhydrophobic. Alternatively, even when the solvent is hydrophilic, thesolvent can be used by mixing with a hydrophobic solvent before use.

In a preferred embodiment, for example, such organic solvents include1-heptanol as a hydrophobic solvent and tetrahydrofuran as a hydrophilicsolvent. When the above organic solvents include tetrahydrofuran and1-heptanol, a volume ratio “tetrahydrofuran:1-heptanol” is preferably0.1 to 10:1 from the viewpoint of the adjustment of the shapes andorganic substance content of the beads of the present invention; thevolume ratio “tetrahydrofuran:1-heptanol” is particularly preferably4:1.

Further, examples of proton-donating solvents include ethanol,1-propanol, 2-propanol, 1-butyl alcohol, 2-butyl alcohol, isobutylalcohol, tert-butyl alcohol, cyclohexanol, and methanol.

In addition, from the viewpoints of improvements in solvent resistanceand mechanical strength of each of the beads, and the maintenance of theability of the beads to separate optical isomers, the followingoperation may be further performed in addition to the above operations:silanol groups remaining on the resultant beads are subjected to endcapping with a proper solvent and a silane coupling agent after anoperation in which the beads are dried and dispersed in a proper solventso that a crosslinking reaction in the beads may be performed has beenperformed or without the performance of such crosslinking reaction.

The beads in the present invention each have a particle size oftypically 1 to 500 μm, preferably 5 to 300 μm, or particularlypreferably 5 to 100 μm. As long as the particle size falls within suchrange, the ratio at which a column or the like is filled with the beads(filling rate) can be increased, and hence the ability of the resultantproduct to separate optical isomers can be improved. In addition, thebeads in the present application may be either porous or nonporous, butare preferably porous and have an average pore size of 10 to 10,000 Å,or preferably 50 to 5,000 Å. An average pore size within such range ispreferable because a solution containing optical isomers sufficientlypermeates into the pores, and the ability of the beads to separate theoptical isomers can be improved.

The particle sizes of the beads obtained by the above-mentioned methodcan be adjusted by adopting the following procedure in theabove-mentioned method: adjusting a ratio between the amounts of theorganic solvent and the aqueous solution of the surfactant or thesolvent containing the proton-donating solvent, adjusting theconcentration of the polymer compound derivative such as apolysaccharide derivative, adjusting the speed at which the organicsolvent is added to the aqueous solution of the surfactant or thesolvent containing the proton-donating solvent, and considering thecapacity and shape of a stirring container and the shape of a stirringblade, appropriately changing the speed at which the aqueous solution ofthe surfactant or the solvent containing the proton-donating solvent isstirred within the range of 800 to 3,000 rpm.

The beads of the present invention can be used as a filler for opticalisomer separation not only for HPLC but also for chromatography wherehigh pressure resistance is needed such as supercritical fluidchromatography. When the complex of the present invention is used in abead form, as described above, a crosslinking reaction occurs at thetime of the formation of the beads, and a three-dimensionallycrosslinked structure may be present in each of the beads. As a result,the mechanical strength of each of the beads is improved. In addition,an optical isomer separating column filled with the beads as aseparating agent for optical isomers by a known method can opticallyresolve increased amounts of optical isomers in one stroke because thecontent of the above polymer compound derivative in the beads is largerthan a conventional one as described above. As a result, the opticalisomer separating column has an excellent ability to separate opticalisomers.

In addition, as described above, the crosslinking reaction between thebeads occurs simultaneously with the formation of the beads, so there isno need to prompt the crosslinking reaction after the formation of thebeads, and a time period for production steps for the filler for opticalisomer separation is significantly shortened. As described above, incase of necessity, the solvent resistance and mechanical strength ofeach of the beads can be additionally improved by properly treating thebeads after the preparation of the beads to promote a crosslinkingreaction between unreacted Y's in the compound represented by theabove-mentioned general formula (I) introduced into the polymer compoundderivative.

<6> Separating Agent for Optical Isomers Formed of Complex of thePresent Invention

The complex of the present invention is preferably produced in a beadform through the above operations, and the beads can be used as aseparating agent for optical isomers. When the above beads are used as aseparating agent for optical isomers in HPLC or supercritical fluidchromatography, the beads can be used after a column has been filledwith the beads by a known method (such as a slurry method).

In addition to the above-mentioned HPLC and supercritical fluidchromatography, the separating agent for optical isomers using thecomplex formed as beads of the present invention can be used also as afiller for a capillary column for gas chromatography or electrophoresis,or particularly capillary electrochromatography (CEC), capillary zoneelectrophoresis (CZE), or micellar electrokinetic chromatography (MEKC).

Hereinafter, examples embodying the present invention are described, butthe present invention is not limited to those examples.

Examples Example 1

(1-1) Synthesis of Cellulose 3,5-dimethylphenylcarbamate havingAlkoxysilyl Groups

First, 4.00 g (24.7 mmol) of dried cellulose were dissolved in a mixedsolution of 120 ml of dehydrated N,N-dimethylacetamide, 60 ml ofdehydrated pyridine, and 8.00 g of lithium chloride.

Then, 9.08 g (61.8 mmol) of 3,5-dimethylphenyl isocyanate were added tothe resultant solution, and the mixture was subjected to a reaction at80° C. for 15 hours. After that, 0.52 g (2.1 mmol) of3-isocyanatepropyltriethoxysilane was added to the resultant, and themixture was subjected to a reaction at 80° C. for 12 hours. Further,9.08 g (61.8 mmol) of 3,5-dimethylphenyl isocyanate were added to theresultant, and the mixture was subjected to a reaction at 80° C. for 11hours. A pyridine soluble portion was dropped into methanol andrecovered as an insoluble portion. After that, the portion was dried ina vacuum. As a result, 13.13 g of a cellulose3,5-dimethylphenylcarbamate derivative A into which alkoxysilyl groupshad been introduced were obtained. The following analysis confirmed thatthe introduction ratios of 3,5-dimethylphenyl isocyanate and thealkoxysilyl groups were 97.7% and 2.3%, respectively (see FIG. 6).

(1-2) Measurement of Ratio of Introduction of Molecules of3-isocyanatepropyltriethoxysilane in Cellulose Derivative

The ratio of introduction of silyl groups in the polymer compoundderivative was calculated from a ratio between a proton of the phenylgroup of a 3,5-dimethylphenyl group of the cellulose derivative intowhich the silyl groups had been introduced and a methylene protondirectly bonded to silicon of a 3-triethoxysilylpropyl group determinedfrom a ¹H NMR spectrum (400 MHz, Gemini-2000 (manufactured by Varian,Inc.), in DMSO-d₆, 80° C.), and was defined as the ratio of introductionof molecules of 3-isocyanatepropyltriethoxysilane in the polymercompound derivative. FIG. 6 shows the ¹H NMR spectrum of thederivative-A. The ¹H NMR spectrum shows that a signal derived from theproton of the phenyl group appears at around 6.0 to 7.0 ppm and that asignal derived from the methylene proton bonded to a silyl group appearsat around 0.5 ppm. Therefore, the ¹H NMR results confirmed that theratio of introduction of the molecules of 3,5-dimethylphenyl isocyanateand the ratio of introduction of the molecules of3-isocyanatepropyltriethoxysilane were 97.7% and 2.3%, respectively.

(1-3) Preparation of Cellulose Derivative Beads

First, 250 mg of the derivative A, 4 ml of tetraethoxysilane (TEOS), 1ml of water, and 0.5 ml of chlorotrimethylsilane were dissolved in 30 mlof a mixed solvent containing tetrahydrofuran/1-heptanol (4/1, v/v).After having been heated at 80° C. for 9 hours, the solution was droppedto 500 ml of a 0.2% aqueous solution of sodium dodecylsulfate heated ina water bath at 80° C. while the aqueous solution was stirred with adisperser at a shaft revolution number of 1,100 rpm. After the dropping,the mixture was stirred at 80° C. for 1 hour, and the resultantsuspension was passed through a 20-μm filter so that beads each having alarge particle diameter might be removed. The suspension after havingbeen passed through the filter was subjected to suction filtration sothat hybrid beads might be recovered. Then, the hybrid beads were washedwith water and methanol. After the washing, the washed beads were driedin a vacuum. As a result, 368 mg of hybrid beads were obtained. As aresult of the repetition of the foregoing operations, hybrid beads-A-1each having a particle diameter of about 10 μm were recovered. Thethermogravimetric analysis (SSC-5200, Seiko Instruments Inc.) of theresultant hybrid beads-A-1 confirmed that an organic substance ratio was45 wt %. A six-blade type disperser shaft and a one-liter beaker wereused in the preparation of the beads.

Then, 2.1 g of the dried hybrid beads A-1 were dispersed in a mixture“ethanol/water/chlorotrimethylsilane (21 ml/5.25 ml/0.35 ml)”, and thedispersion liquid was subjected to a reaction for 1 hour while beingrefluxed in an oil bath at 100° C. Thus, crosslinking in the beads wasperformed. Then, 2.0 g of hybrid beads A-2 thus obtained were dispersedin a mixture “toluene/pyridine/chlorotrimethylsilane/hexamethyldisilazane (16.7 ml/16.7 ml/0.31ml/0.64 ml)”, and the dispersion liquid was subjected to a reaction inan oil bath at 80° C. for 30 minutes so that the remaining silanolgroups might be subjected to end capping. Hybrid beads A-3 thus obtainedwere washed with 1.95 g of acetone. As a result, 28 mg of the cellulosederivative were dissolved, but the organic substance ratio was kept at45 wt % (confirmed by thermogravimetric analysis). The beads after thewashing with acetone are defined as hybrid beads A-4. The resultantbeads were observed with a scanning electron microscope (SEM) (JSM-5600manufactured by JEOL Ltd.). As a result, it was found that none of thesizes and surface states of the beads showed a certain change even afterthe beads had been impregnated with acetone. FIG. 2 shows the SEM imagesof the hybrid beads A-4 before and after washing with acetone.

(1-4) Filling of Column

The hybrid beads A-4 thus obtained were subjected to particle sizefractionation, and was then loaded into a stainless steel column havinga length of 25 cm and an inner diameter of 0.2 cm by a slurry method,whereby a column-1 was obtained.

The column-1 had a number of theoretical plates (N) of 850.

(1-5) Evaluation for Optical Resolution using HPLC

As shown in FIG. 4, the optical resolution of ten kinds of racemicbodies (1 to 10) with the column-1 obtained by the above-mentionedoperation (column temperature: about 20° C.) was performed. A HPLC pump(trade name: PU-980) manufactured by JASCO Corporation was used. Thedetection and identification of a peak were performed with a UV detector(wavelength: 254 nm, trade name: UV-970, manufactured by JASCOCorporation) and an optical rotation detector (trade name: OR-990,manufactured by JASCO Corporation) under the following conditions: amixture hexane/2-propanol (90/10, v/v) was used as an eluent, and itsflow rate was 0.2 ml/min. It should be noted that the number oftheoretical plates N was determined from the peak of benzene, and a timet₀ for which the eluent passed through the column was determined fromthe elution time of 1,3,5-tri-tert-butylbenzene. It should be noted thatconditions concerning, for example, HPLC and a detector used in theevaluation for optical resolution identical to those described abovewere used in the following examples and comparative examples.

Table 1 shows the results of the optical resolution with the column-1.Values in the table are a capacity ratio k1′ and a separation factor α,and a sign in parentheses represents the optical activity of anenantiomer which was previously eluted.

It should be noted that the capacity ratio k1′ and the separation factorα are defined by the following formulae. A capacity ratio and aseparation factor were calculated in the following examples andcomparative examples by using the same formulae.

[Eq. 4]

Capacity ratio k1′

k1′=[(retention time of enantiomer)−(t ₀)]/t ₀

[Eq. 5]

Separation factor α

α=(capacity ratio of enantiomer to be retained more strongly)/(capacityratio of enantiomer to be retained more weakly)

(1-6) Evaluation for Optical Resolving Ability by Supercritical FluidChromatography (SFC)

The molecules of a racemic body 11 (warfarin) illustrated in FIG. 4 wereoptically separated by SFC with the column-1 obtained by the aboveoperations. An SFC apparatus used included pumps available under theproduct names of PU-2080 and PU-2086 from JASCO Corporation, a columnthermostat available under the product name of CO-1560 from JASCOCorporation, and a back pressure controller available under the productname of 880-81 from JASCO Corporation. Carbon dioxide was used as aneluent, and ethanol was added as a modifier. The flow rates of carbondioxide and ethanol were set to 0.5 ml/min and 0.1 ml/min, respectively,and a column temperature and a back pressure were set to 40° C. and 100kg/cm², respectively. The detection and identification of a peak wereperformed with a UV detector (wavelength: 254 nm, product name: UV-2075,manufactured by JASCO Corporation). FIG. 5 illustrates the results ofthe optical resolution with the column-1. In addition, FIG. 3illustrates the SEM images of the beads A-4 before and after use insupercritical fluid chromatography (SFC).

Example 2

(2-1) Synthesis of Cellulose 3,5-dimethylphenylcarbamate havingAlkoxysilyl Groups

First, 4.00 g (24.7 mmol) of dried cellulose were dissolved in a mixedsolution of 120 ml of dehydrated N,N-dimethylacetamide, 60 ml ofdehydrated pyridine, and 8.00 g of lithium chloride.

Then, 9.08 g (61.8 mmol) of 3,5 -dimethylphenyl isocyanate were added tothe resultant solution, and the mixture was subjected to a reaction at80° C. for 15 hours. After that, 0.34 g (1.4 mmol) of3-isocyanatepropyltriethoxysilane was added to the resultant, and themixture was subjected to a reaction at 80° C. for 12 hours. Further,9.08 g (61.8 mmol) of 3,5-dimethylphenyl isocyanate were added to theresultant, and the mixture was subjected to a reaction at 80° C. for 11hours. A pyridine soluble portion was dropped into methanol andrecovered as an insoluble portion. After that, the portion was dried ina vacuum. As a result, 13.29 g of a cellulose3,5-dimethylphenylcarbamate derivative B into which alkoxysilyl groupshad been introduced were obtained. The results of ¹H NMR confirmed thatthe introduction ratios of 3,5-dimethylphenyl isocyanate and thealkoxysilyl groups were 98.6% and 1.4%, respectively (see FIG. 7).

(2-2) Preparation of Cellulose Derivative Beads

First, 250 mg of the derivative B, 3.5 ml of tetraethoxysilane (TEOS), 1ml of water, and 0.5 ml of chlorotrimethylsilane were dissolved in 30 mlof a mixed solvent containing tetrahydrofuran/1-heptanol (4/1, v/v).After having been heated at 80° C. for 9 hours, the solution was droppedto 500 ml of a 0.2% aqueous solution of sodium dodecylsulfate heated ina water bath at 80° C. while the aqueous solution was stirred with adisperser at a shaft revolution number of 1,100 rpm. After the dropping,the mixture was stirred at 80° C. for 1 hour, and the resultantsuspension was passed through a 20-μm filter so that beads each having alarge particle diameter might be removed. The suspension after havingbeen passed through the filter was subjected to suction filtration sothat hybrid beads might be recovered. Then, the hybrid beads were washedwith water and methanol. After the washing, the washed beads were driedin a vacuum. As a result, 285 mg of hybrid beads were obtained. As aresult of the repetition of the foregoing operations, hybrid beads-B-1each having a particle diameter of about 10 μm were recovered. Thethermogravimetric analysis of the resultant hybrid beads-B-1 confirmedthat an organic substance ratio was 55 wt %. A six-blade type dispersershaft and a one-liter beaker were used in the preparation of the beads.

Then, 0.75 g of the dried hybrid beads B-1 were dispersed in a mixture“ethanol/water/chlorotrimethylsilane (7.5 m1/1.9 m1/0.13 ml)”, and thedispersion liquid was subjected to a reaction for 1 hour while beingrefluxed in an oil bath at 100° C. Thus, crosslinking in the beads wasperformed. Then, 0.6 g of hybrid beads B-2 thus obtained were dispersedin a mixture“toluene/pyridine/chlorotrimethylsilane/hexamethyldisilazane (5.0 ml/5.0ml/1.25 ml/0.07 ml)”, and the dispersion liquid was subjected to areaction in an oil bath at 110° C. for 15 minutes so that the remainingsilanol groups might be subjected to end capping. The beads thusobtained are hereby referred to as hybrid beads B-3. FIG. 2 shows theSEM images of the hybrid beads B-3.

(2-3) Filling of Column

The hybrid beads B-3 thus obtained were subjected to particle sizefractionation, and was then loaded into a stainless steel column havinga length of 25 cm and an inner diameter of 0.2 cm by a slurry method,whereby a column-2 was obtained.

The column-2 had a number of theoretical plates (N) of 1,100.

(2-4) Evaluation for Optical Resolution

As shown in FIG. 4, the optical resolution of ten kinds of racemicbodies (1 to 10) with the column-2 obtained by the above-mentionedoperation was performed. The detection and identification of a peak wereperformed with a UV detector and an optical rotation detector under thefollowing conditions: a mixture hexane/2-propanol (90/10, v/v) was usedas an eluent, and its flow rate was 0.2 ml/min. It should be noted thatthe number of theoretical plates N was determined from the peak ofbenzene, and a time t₀ for which the eluent passed through the columnwas determined from the elution time of 1,3,5-tri-tert-butylbenzene.Table 1 shows the results of the optical resolution with the column-2.Values in the table are a capacity ratio k1′ and a separation factor α,and a sign in parentheses represents the optical activity of anenantiomer which was previously eluted.

Example 3

(3-1) Synthesis of Cellulose 3,5-dimethylphenylcarbamate havingAlkoxysilyl Groups

First, 0.50 g (3.09 mmol) of dried cellulose was dissolved in a mixedsolution of 15 ml of dehydrated N,N-dimethylacetamide, 7.5 ml ofdehydrated pyridine, and 1.00 g of lithium chloride.

Then, 1.13 g (7.72 mmol) of 3,5-dimethylphenyl isocyanate were added tothe resultant solution, and the mixture was subjected to a reaction at80° C. for 6 hours. After that, 84 mg (0.34 mmol) of3-isocyanatepropyltriethoxysilane was added to the resultant, and themixture was subjected to a reaction at 80° C. for 13 hours. Further,1.36 g (9.26 mmol) of 3,5-dimethylphenyl isocyanate were added to theresultant, and the mixture was subjected to a reaction at 80° C. for 7hours. A pyridine soluble portion was dropped into methanol andrecovered as an insoluble portion. After that, the portion was dried ina vacuum. As a result, 1.65 g of a cellulose 3,5-dimethylphenylcarbamatederivative C into which alkoxysilyl groups had been introduced wereobtained. The results of ¹H NMR confirmed that the introduction ratiosof 3,5-dimethylphenyl isocyanate and the alkoxysilyl groups were 97.3%and 2.7%, respectively (see FIG. 8).

(3-2) Preparation of Cellulose Derivative Beads

First, 250 mg of the derivative C, 2.25 ml of tetraethoxysilane (TEOS),1 ml of water, and 0.5 ml of chlorotrimethylsilane were dissolved in 30ml of a mixed solvent containing tetrahydrofuran/1-heptanol (4/1, v/v).After having been heated at 80° C. for 9 hours, the solution was droppedto 500 ml of a 0.2% aqueous solution of sodium dodecylsulfate heated ina water bath at 80° C. while the aqueous solution was stirred with adisperser at a shaft revolution number of 1,100 rpm. After the dropping,the mixture was stirred at 80° C. for 1 hour, and the resultantsuspension was passed through a 20-μm filter so that beads each having alarge particle diameter might be removed. The suspension after havingbeen passed through the filter was subjected to suction filtration sothat hybrid beads might be recovered. Then, the hybrid beads were washedwith water and methanol. After the washing, the washed beads were driedin a vacuum. As a result, 297 mg of hybrid beads were obtained. As aresult of the repetition of the foregoing operations, hybrid beads-C-1each having a particle diameter of about 3 to 10 μm were recovered. Thethermogravimetric analysis of the resultant hybrid beads-C-1 confirmedthat an organic substance ratio was 62 wt %. A six-blade type dispersershaft and a one-liter beaker were used in the preparation of the beads.

Then, 0.85 g of the dried hybrid beads C-1 was dispersed in a mixture“ethanol/water/chlorotrimethylsilane (9.0 ml/2.25 ml/0.15 ml)”, and thedispersion liquid was subjected to a reaction for 1 hour while beingrefluxed in an oil bath at 100° C. Thus, crosslinking in the beads wasperformed. Then, 0.7 g of hybrid beads C-2 thus obtained was dispersedin a mixture“toluene/pyridine/chlorotrimethylsilane/hexamethyldisilazane (5.0 ml/5.0ml/0.08 ml/1.30 ml)”, and the dispersion liquid was subjected to areaction in an oil bath at 110° C. for 30 minutes so that the remainingsilanol groups might be subjected to end capping. The beads thusobtained are hereby referred to as hybrid beads C-3. FIG. 2 shows theSEM images of the hybrid beads C-3.

(3-3) Filling of Column

The hybrid beads C-3 thus obtained were subjected to particle sizefractionation, and was then loaded into a stainless steel column havinga length of 25 cm and an inner diameter of 0.2 cm by a slurry method,whereby a column-3 was obtained.

The column-3 had a number of theoretical plates (N) of 200.

(3-4) Evaluation for Optical Resolution

As shown in FIG. 4, the optical resolution of ten kinds of racemicbodies (1 to 10) with the column-3 obtained by the above-mentionedoperation was performed. The detection and identification of a peak wereperformed with a UV detector and an optical rotation detector under thefollowing conditions: a mixture hexane/2-propanol (90/10, v/v) was usedas an eluent, and its flow rate was 0.2 ml/min. It should be noted thatthe number of theoretical plates N was determined from the peak ofbenzene, and a time t₀ for which the eluent passed through the columnwas determined from the elution time of 1,3,5-tri-tert-butylbenzene.Table 1 shows the results of the optical resolution with the column-3.Values in the table are a capacity ratio k1′ and a separation factor α,and a sign in parentheses represents the optical activity of anenantiomer which was previously eluted.

Example 4

The following experiment was performed in order that an organicsubstance content in beads when no polymer compound derivative was usedmight be calculated.

First, 5 ml of tetraethoxysilane (TEOS), 1 ml of water, and 0.5 ml ofchlorotrimethylsilane were dissolved in 30 ml of a mixed solventcontaining tetrahydrofuran/1-heptanol (4/1, v/v). After having beenheated at 80° C. for 9 hours, the solution was dropped to 500 ml of a0.2% aqueous solution of sodium dodecylsulfate heated in a water bath at80° C. while the aqueous solution was stirred with a disperser at ashaft revolution number of 1,100. rpm. After the dropping, the mixturewas stirred at 80° C. for 1 hour. The resultant suspension was subjectedto suction filtration so that a silica gel-1 might be recovered. Then,the silica gel was washed with water and methanol. After the washing,the washed silica gel was dried in a vacuum. As a result, 360 mg of thesilica gel-1 were obtained. The thermogravimetric analysis (SSC-5200,Seiko Instruments Inc.) of the resultant silica gel-1 confirmed that theorganic substance ratio was 10 wt %. A six-blade type disperser shaftand a one-liter beaker were used in the preparation of the silica gelbeads.

Example 5

(5-1) Synthesis of Cellulose 3,5-dimethylphenylcarbamate havingAlkoxysilyl Groups

First, 4.00 g (24.7 mmol) of dried cellulose were dissolved in a mixedsolution of 120 ml of dehydrated N,N-dimethylacetamide, 60 ml ofdehydrated pyridine, and 8.00 g of lithium chloride.

Then, 9.08 g (61.8 mmol) of 3,5-dimethylphenyl isocyanate were added tothe resultant solution, and the mixture was subjected to a reaction at80° C. for 11 hours. After that, 0.38 g (1.56 mmol) of3-isocyanatepropyltriethoxysilane was added to the resultant, and themixture was subjected to a reaction at 80° C. for 12 hours. Further,12.7 g (86.4 mmol) of 3,5-dimethylphenyl isocyanate were added to theresultant, and the mixture was subjected to a reaction at 80° C. for 10hours. A pyridine soluble portion was dropped into methanol andrecovered as an insoluble portion. After that, the portion was dried ina vacuum. As a result, 12.9 g of a cellulose 3,5-dimethylphenylcarbamatederivative D into which alkoxysilyl groups had been introduced wereobtained. The introduction ratios of 3,5-dimethylphenyl isocyanate andthe alkoxysilyl groups were 98.3% and 1.7%, respectively.

(5-2) Preparation of Cellulose Derivative Beads

First, 250 mg of the derivative D, 3 ml of tetraethoxysilane (TEOS), 1ml of water, and 0.5 ml of chloromethylsilane were dissolved in 30 ml ofa mixed solution containing tetrahydrofuran/1-heptanol (4/1, v/v). Afterhaving been heated at 80° C. for 9 hours, the solution was dropped to500 ml of a 0.4% aqueous solution of trimethyloctadecylammonium chlorideheated in a water bath at 80° C. while the aqueous solution was stirredwith a disperser at a shaft revolution number of 1,100 rpm. After thedropping, the mixture was stirred at 80° C. for 1 hour, and theresultant suspension was subjected to suction filtration so that hybridbeads might be recovered. Then, the hybrid beads were washed with waterand methanol. After the washing, the washed beads were dried in avacuum. As a result, 1,452 mg of hybrid beads D-1 were obtained. As aresult of the repetition of the foregoing operations, hybrid beads D-2each having a particle diameter of about 10 μm were recovered. Thethermogravimetric measurement (SSC-5200, Seiko Instruments Inc.) of theresultant hybrid beads D-2 confirmed that an organic substance ratio was28 wt %. A six-blade type disperser shaft and a one-liter beaker wereused in the preparation of the beads.

Then, 1.0 g of the dried hybrid beads D-2 was dispersed in a mixedsolvent “toluene/pyridine/chlorotrimethylsilane/hexamethyldisilazane (15ml/15 ml/0.20 ml/0.42 ml)”, and the dispersion liquid was subjected to areaction in an oil bath at 80° C. for 30 minutes so that the remainingsilanol groups might be subjected to end capping. Hybrid beads D-3 thusobtained were washed with water and methanol. As a result, 1.02 g of thefinal product (hybrid beads D-4) were obtained. The organic substanceratio of the hybrid beads D-4 was 30%.

(5-3) Filling of Column

A column-4 was obtained by filling the same column as that of the abovesection (1-4) with the resultant hybrid beads D-4 by the same method asthat described in the above section (1-4).

(5-4) Evaluation for Optical Resolving Ability

Evaluation for optical resolving ability was performed with the column-4obtained by the above operations by the same method as that described inthe above section (1-5). Table 2 shows the results of the evaluation.

Example 6

(6-1) Preparation of Cellulose Derivative Beads

First, 250 mg of the derivative D, 2 ml of tetraethoxysilane (TEOS), 1ml of water, and 0.5 ml of chloromethylsilane were dissolved in 30 ml ofa mixed solution containing tetrahydrofuran/1-heptanol (4/1, v/v). Afterhaving been heated at 80° C. for 9 hours, the solution was dropped to500 ml of a 0.4% aqueous solution of trimethyloctadecylammonium chlorideheated in a water bath at 80° C. while the aqueous solution was stirredwith a disperser at a shaft revolution number of 1,100 rpm. After thedropping, the mixture was stirred at 80° C. for 1 hour, and theresultant suspension was subjected to suction filtration so that hybridbeads might be recovered. Then, the hybrid beads were washed with waterand methanol. After the washing, the washed beads were dried in avacuum. As a result, 1,054 mg of hybrid beads D-5 were obtained. As aresult of the repetition of the foregoing operations, hybrid beads D-6each having a particle diameter of about 10 μm were recovered. Thethermogravimetric measurement (SSC-5200, Seiko Instruments Inc.) of theresultant hybrid beads D-6 confirmed that an organic substance ratio was35 wt %. A six-blade type disperser shaft and a one-liter beaker wereused in the preparation of the beads.

Then, 3.0 g of the dried hybrid beads D-6 were dispersed in a mixture“toluene/pyridine/hexamethyldisilazane (15 ml/15 ml/8.9 ml)”, and thedispersion liquid was subjected to a reaction in an oil bath at 80° C.for 15 hours so that the remaining silanol groups might be subjected toend capping. Hybrid beads D-7 thus obtained were washed with water andmethanol. As a result, 2.89 g of the final product (hybrid beads D-8)were obtained. The organic substance ratio of the hybrid beads D-8 was34%.

(6-2) Filling of Column

The hybrid beads D-8 thus obtained were subjected to particle sizefractionation, and was then loaded into a stainless steel column havinga length of 25 cm and an inner diameter of 0.46 cm by a slurry method,whereby a column-5 was obtained.

(6-3) Evaluation for Optical Resolving Ability

Ten kinds of racemic bodies (1 to 10) illustrated in FIG. 4 wereoptically separated with the column-5 obtained by the above operations.A mixture containing hexane/2-propanol (90/10, v/v) was used as aneluent, and its flow rate was set to 1.0 ml/min. Then, the detection andidentification of a peak were performed with the same UV detector andoptical rotatory detector as those of the above section (1-5). Table 2shows the results of the evaluation.

Example 7 (7-1) Synthesis of Amylose 3,5-dimethylphenylcarbamate havingAlkoxysilyl Groups

First, 1.50 g (9.26 mmol) of dried amylose were dissolved in a mixedsolution of 45 ml of dehydrated N,N-dimethylacetamide, 22.5 ml ofdehydrated pyridine, and 3.00 g of lithium chloride.

Then, 3.41 g (23.2 mmol) of 3,5-dimethylphenyl isocyanate were added tothe resultant solution, and the mixture was subjected to a reaction at80° C. for 6 hours. After that, 0.16 g (0.65 mmol) of3-isocyanatepropyltriethoxysilane was added to the resultant, and themixture was subjected to a reaction at 80° C. for 13 hours. Further,3.41 g (23.2 mmol) of 3,5-dimethylphenyl isocyanate were added to theresultant, and the mixture was subjected to a reaction at 80° C. for 10hours. A pyridine soluble portion was dropped into methanol andrecovered as an insoluble portion. After that, the portion was dried ina vacuum. As a result, 5.40 g of an amylose 3,5-dimethylphenylcarbamatederivative E into which alkoxysilyl groups had been introduced wereobtained. The introduction ratios of 3,5-dimethylphenyl isocyanate andthe alkoxysilyl groups were 98.3% and 1.7%, respectively.

(7-2) Preparation of Amylose Derivative Beads

First, 250 mg of the derivative E, 4 ml of tetraethoxysilane (TEOS), 1ml of water, and 0.5 ml of chloromethylsilane were dissolved in 30 ml ofa mixed solution containing tetrahydrofuran/1-heptanol (4/1, v/v). Afterhaving been heated at 80° C. for 9 hours, the solution was dropped to500 ml of a 0.2% aqueous solution of sodium dodecylsulfate heated in awater bath at 80° C. while the aqueous solution was stirred with adisperser at a shaft revolution number of 1,100 rpm. After the dropping,the mixture was stirred at 80° C. for 1 hour, and the resultantsuspension was passed through a 20-μm filter so that beads each having alarge particle diameter might be removed. The suspension after havingbeen passed through the filter was subjected to suction filtration sothat hybrid beads might be recovered. Then, the hybrid beads were washedwith water and methanol. After the washing, the washed beads were driedin a vacuum. As a result, 1,775 mg of hybrid beads E-1 were obtained. Asa result of the repetition of the foregoing operations, hybrid beads E-2each having a particle diameter of about 10 μm were recovered. Thethermogravimetric measurement (SSC-5200, Seiko Instruments Inc.) of theresultant hybrid beads E-2 confirmed that an organic substance ratio was31 wt %. A six-blade type disperser shaft and a one-liter beaker wereused in the preparation of the beads.

Then, 0.75 g of the dried hybrid beads E-2 were dispersed in 9.5 ml of amixed solution “ethanol/water/chlorotrimethylsilane (6/1.5/0.1(v/v/v))”,and the dispersion liquid was subjected to a reaction for 1 hour whilebeing refluxed in an oil bath at 100° C. Thus, crosslinking in the beadswas performed. Then, 0.70 g of hybrid beads E-3 thus obtained weredispersed in a mixture“toluene/pyridine/chlorotrimethylsilane/hexamethyldisilazane (5.8 ml/5.8ml/0.28 ml/0.14 ml)”, and the dispersion liquid was subjected to areaction in an oil bath at 80° C. for 30 minutes so that the remainingsilanol groups might be subjected to end capping. Hybrid beads E-4 thusobtained were washed with water and methanol. As a result, 0.68 g of thefinal product (hybrid beads E-5) were obtained.

(7-3) Filling of Column

A column-6 was obtained by filling the same column as that of the abovesection (1-4) with the resultant hybrid beads E-5 by the same method asthat described in the above section (1-4).

(7-4) Evaluation for Optical Resolving Ability

Evaluation for optical resolving ability was performed with the column-6obtained by the above operations by the same method as that described inthe above section (1-5). Table 3 shows the results of the evaluation.

Example 8

(8-1) Preparation of Amylose Derivative Beads

First, 250 mg of the derivative E, 3 ml of tetraethoxysilane (TEOS), 1ml of water, and 0.5 ml of chloromethylsilane were dissolved in 30 ml ofa mixed solution containing tetrahydrofuran/1-heptanol (4/1, v/v). Afterhaving been heated at 80° C. for 9 hours, the solution was dropped to500 ml of a 0.2% aqueous solution of sodium dodecylsulfate heated in awater bath at 80° C. while the aqueous solution was stirred with adisperser at a shaft revolution number of 1,100 rpm. After the dropping,the mixture was stirred at 80° C. for 1 hour, and the resultantsuspension was passed through a 20-μm filter so that beads each having alarge particle diameter might be removed. The suspension after havingbeen passed through the filter was subjected to suction filtration sothat hybrid beads might be recovered. Then, the hybrid beads were washedwith water and methanol. After the washing, the washed beads were driedin a vacuum. As a result, 0.61 mg of hybrid beads E-6 were obtained. Asa result of the repetition of the foregoing operations, hybrid beads E-7each having a particle diameter of about 10 μm were recovered. Thethermogravimetric measurement (SSC-5200, Seiko Instruments Inc.) of theresultant hybrid beads E-7 confirmed that an organic substance ratio was48 wt %. A six-blade type disperser shaft and a one-liter beaker wereused in the preparation of the beads.

Then, 0.60 g of the dried hybrid beads E-7 were dispersed in 7.6 ml of amixed solution “ethanol/water/chlorotrimethylsilane (6/1.5/0.1(v/v/v))”,and the dispersion liquid was subjected to a reaction for 1 hour whilebeing refluxed in an oil bath at 100° C. Thus, crosslinking in the beadswas performed. Then, 0.58 g of hybrid beads E-8 thus obtained weredispersed in a mixture“toluene/pyridine/chlorotrimethylsilane/hexamethyldisilazane (4.8 ml/4.8ml/0.18 ml/0.09 ml)”, and the dispersion liquid was subjected to areaction in an oil bath at 80° C. for 30 minutes so that the remainingsilanol groups might be subjected to end capping. Hybrid beads E-9 thusobtained were washed with water and methanol. As a result, 0.55 g of thefinal product (hybrid beads E-10) were obtained.

(8-2) Filling of Column

A column-7 was obtained by filling the same column as that of the abovesection (1-4) with the resultant hybrid beads E-10 by the same method asthat described in the above section (1-4).

(8-3) Evaluation for Optical Resolving Ability

Evaluation for optical resolving ability was performed with the column-7obtained by the above operations by the same method as that described inthe above section (1-5). Table 3 shows the results of the evaluation.

Example 9 (9-1) Synthesis of Cellulose 3,5-dimethylphenylcarbamatehaving Alkoxysilyl Groups

First, 8.00 g (49.4 mmol) of dried cellulose were dissolved in a mixedsolution of 240 ml of dehydrated N,N-dimethylacetamide, 120 ml ofdehydrated pyridine, and 16.0 g of lithium chloride.

Then, 18.2 g (124 mmol) of 3,5-dimethylphenyl isocyanate were added tothe resultant solution, and the mixture was subjected to a reaction at80° C. for 6 hours. After that, 0.73 g (2.97 mmol) of3-isocyanatepropyltriethoxysilane was added to the resultant, and themixture was subjected to a reaction at 80° C. for 12 hours. Further,25.4 g (173 mmol) of 3,5-dimethylphenyl isocyanate were added to theresultant, and the mixture was subjected to a reaction at 80° C. for 8hours. A pyridine soluble portion was dropped into methanol andrecovered as an insoluble portion. After that, the portion was dried ina vacuum. As a result, 25.1 g of a cellulose 3,5-dimethylphenylcarbamatederivative F into which alkoxysilyl groups had been introduced wereobtained. The introduction ratios of 3,5-dimethylphenyl isocyanate andthe alkoxysilyl groups were 98.3% and 1.7%, respectively.

(9-2) Preparation of Cellulose Derivative Beads

First, 250 mg of the derivative F, 1 ml of tetraethoxysilane (TEOS),0.83 ml of 1,2-bistriethoxysilylethane (BTSE), 1 ml of water, and 0.5 mlof chloromethylsilane were dissolved in 30 ml of a mixed solutioncontaining tetrahydrofuran/1-heptanol (4/1, v/v). After having beenheated at 80° C. for 9 hours, the solution was dropped to 500 ml of a0.2% aqueous solution of sodium dodecylsulfate heated in a water bath at80° C. while the aqueous solution was stirred with a disperser at ashaft revolution number of 1,100 rpm. After the dropping, the mixturewas stirred at 80° C. for 1 hour, and the resultant suspension wassubjected to suction filtration so that hybrid beads might be recovered.Then, the hybrid beads were washed with water and methanol. After thewashing, the washed beads were dried in a vacuum. As a result, 680 mg ofhybrid beads F-1 were obtained. As a result of the repetition of theforegoing operations, hybrid beads F-2 each having a particle diameterof about 10 μm were recovered. The thermogravimetric measurement(SSC-5200, Seiko Instruments Inc.) of the resultant hybrid beads F-2confirmed that an organic substance ratio was 48 wt %. A six-blade typedisperser shaft and a one-liter beaker were used in the preparation ofthe beads.

(9-3) Filling of Column

A column-8 was obtained by filling the same column as that of the abovesection (1-4) with the resultant hybrid beads F-2 by the same method asthat described in the above section (1-4).

(9-4) Evaluation for Optical Resolving Ability

Evaluation for optical resolving ability was performed with the column-8obtained by the above operations by the same method as that described inthe above section (1-5). Table 4 shows the results of the evaluation.

Example 10

(10-1) Preparation of Cellulose Derivative Beads

First, 250 mg of the derivative F, 1.5 ml of tetraethoxysilane (TEOS),0.42 ml of 1,2-bistriethoxysilylethane (BTSE), 1 ml of water, and 0.5 mlof chloromethylsilane were dissolved in 30 ml of a mixed solutioncontaining tetrahydrofuran/1-heptanol (4/1, v/v). After having beenheated at 80° C. for 9 hours, the solution was dropped to 500 ml of a0.2% aqueous solution of sodium dodecylsulfate heated in a water bath at80° C. while the aqueous solution was stirred with a disperser at ashaft revolution number of 1,100 rpm. After the dropping, the mixturewas stirred at 80° C. for 1 hour, and the resultant suspension wassubjected to suction filtration so that hybrid beads might be recovered.Then, the hybrid beads were washed with water and methanol. After thewashing, the washed beads were dried in a vacuum. As a result, 547 mg ofhybrid beads F-3 were obtained. As a result of the repetition of theforegoing operations, hybrid beads F-4 each having a particle diameterof about 10 μm were recovered. The thermogravimetric measurement(SSC-5200, Seiko Instruments Inc.) of the resultant hybrid beads F-4confirmed that an organic substance ratio was 55 wt %. A six-blade typedisperser shaft and a one-liter beaker were used in the preparation ofthe beads.

(10-2) Filling of Column

A column-9 was obtained by filling the same column as that of the abovesection (1-4) with the resultant hybrid beads F-4 by the same method asthat described in the above section (1-4).

(10-3) Evaluation for Optical Resolving Ability

Evaluation for optical resolving ability was performed with the column-9obtained by the above operations by the same method as that described inthe above section (1-5). Table 4 shows the results of the evaluation.

TABLE 1 Racemic Column-1 Column-2 Column-3 body k₁′ α k₁′ α k₁′ α 11.90(−) 1.25 2.29(−) 1.26 2.17(−) 1.24 2 1.47(+) 1.53 1.61(+) 1.731.52(+) 1.63 3 1.10(−) 1.30 1.29(−) 1.46 1.28(−) 1.40 4 1.84(+) 1.242.47(+) 1.17 2.67(+) 1.12 5 2.44(−) 3.49 2.85(−) 3.59 2.89(−) 3.22 63.91(+) 1.24 4.52(+) 1.29 4.41(+) 1.27 7 2.20(−) 1.17 2.53(−) 1.202.64(−) 1.14 8 0.71(+) ~1 0.71(+) 1.17 0.90(+) ~1 9 2.14(−) 2.07 2.58(−)2.17 2.82(−) 2.15 10 1.63(+) ~1 1.62(+) 1.26 2.15 1.0 Eluent:Hexane/2-propanol (90/10, v/v), Column: 25 × 0.20 cm (i.d.) Flow rate:0.20 ml/min.

TABLE 2 Racemic Column-4 Column-5 body k₁′ α k₁′ α 1 1.89(−) ~1 1.35(−)1.17 2 1.49(+) ~1 1.59(+) 1.28 3 0.90(+) ~1 0.74(−) 1.31 4 1.45 1.01.19(+) 1.15 5 2.01(−) 2.79 1.64(−) 3.14 6 3.59(+) ~1 2.26(+) 1.24 72.07 1.0 1.36(−) 1.19 8 0.57 1.0 0.82(+) ~1 9 1.77(−) 1.71 1.39(−) 2.2310 1.02 1.0 0.97(+) 1.31 Column-4: Eluent, Hexane/2-propanol (90/10,v/v), Column: 25 × 0.20 cm (i.d.) Flow rate: 0.20 ml/min Column-5:Eluent, hexane/2-propanol (90/10, v/v), Column: 25 × 0.46 cm (i.d.) Flowrate: 1.0 ml/min

TABLE 3 Racemic Column-6 Column-7 body k₁′ α k₁′ α 1 ~0 1.0 0.76(−) ~1 20.79(+) ~1 0.78(+) 1.40 3 0.35(+) 2.20 0.48(+) 2.28 4 1.44(+) 1.992.04(+) 1.94 5 1.59(−) 2.05 2.26(+) 2.07 6 2.40(−) ~1 3.19(−) 1.08 70.85(+) ~1 1.13(+) 1.13 8 0.23 ~1 0.31(−) ~1 9 0.79(+) 1.0 1.18(+) 1.010 2.29(+) 1.49 3.38(+) 1.76 Eluent: Hexane/2-propanol (90/10, v/v),Column: 25 × 0.20 cm (i.d.) Flow rate: 0.20 ml/min.

TABLE 4 Racemic Column-8 Column-9 body k₁′ α k₁′ α 1 4.09 ~1 3.24(−) ~12 6.87 1.0 5.52(+) ~1 3 1.91(−) 2.30 1.72(−) 2.35 4 2.58 1.0 3.14 1.0 53.17(−) 1.67 3.26(−) 1.97 6 7.45(+) 1.25 6.27(+) 1.36 7 4.54 1.0 3.71(−)1.18 8 4.54 1.0 4.02 1.0 9 4.30(−) 2.23 4.60(−) 2.33 10 2.56 1.0 2.871.0 Eluent: Hexane/2-propanol (90/10, v/v), Column: 25 × 0.20 cm (i.d.)Flow rate: 0.20 ml/min.

1. A complex obtained by causing a polymer compound derivative obtainedby modifying part of hydroxy or amino groups of a polymer compoundhaving the hydroxy or amino groups with a compound represented by thefollowing general formula (I) and one or more kinds of compoundsrepresented by the following general formulae (II) to (V) to react witheach other:[Chem 1]A-X—Si(Y)_(n)R_(3-n)   (I) where A represents a reactive group thatreacts with a hydroxy or amino group, X represents an alkylene groupwhich has 1 to 18 carbon atoms and which may have a branch or an arylenegroup which may have a substituent, Y represents a reactive group thatreacts with a silanol group to form a siloxane bond, R represents analkyl group which has 1 to 18 carbon atoms and which may have a branchor an aryl group which may have a substituent, and n represents aninteger of 1 to 3;[Chem 2]M(OR¹)_(p)R² _(4-n)   (II)[Chem 3]Al(OR¹)_(p)R² _(3-p)   (III)[Chem 4]Mg(OR¹)_(q)R² _(2-q)   (IV) where M represents silicon (Si), titanium(Ti), zirconium (Zr), or chromium (Cr), Al represents aluminum, Mgrepresents magnesium, R¹ represents hydrogen or an alkyl group having 1to 12 carbon atoms, R² represents an alkyl group which has 1 to 18carbon atoms and which may have a branch or an aryl group which may havea substituent, n represents an integer of 1 to 4, p represents aninteger of 1 to 3, and q represents an integer of 1 or 2;[Chem 5][Si(OR³)_(n)R⁴ _(3-n)]—(X)—[Si(OR⁵)_(n)R⁶ _(3-n)]  (V) where R³, R⁴, R⁵,and R⁶ each independently represent an alkyl group which has 1 to 18carbon atoms and which may have a branch or an aryl group which may havea substituent, and X represents an alkylene group which has 1 to 18carbon atoms and which may have a branch or an arylene group which mayhave a substituent.
 2. The complex according to claim 1, wherein thepolymer compound is an optically active organic polymer compound.
 3. Thecomplex according to claim 2, wherein the optically active organicpolymer compound is a polysaccharide.
 4. The complex according to claim3, wherein the polysaccharide is cellulose or amylose.
 5. The complexaccording to claim 1, wherein the compound represented by the generalformula (1) is 3-isocyanatepropyltriethoxysilane,3-isocyanatepropyltrimethoxysilane,3-isocyanatepropyldiethoxymethylsilane,2-isocyanateethyltriethoxysilane, 4-isocyanatephenyltriethoxysilane,3-glycidoxypropyltrimethoxysilane, 3-glycidoxypropyltriethoxysilane, or3-thiocyanatepropyltriethoxysilane.
 6. The complex according to claim 1,wherein a ratio of introduction of the molecules of the compoundrepresented by the general formula (I) into the hydroxy or amino groupsof the polymer compound having the hydroxy or amino groups is 1.0 to35%.
 7. The complex according to claim 1, wherein at least part of thehydroxy or amino groups except the hydroxy or amino groups modified withthe molecules of the compound represented by the general formula (I) arefurther modified with molecules of a compound having a functional groupwhich acts on an optical isomer.
 8. The complex according to claim 7,wherein the molecules of the compound having a functional group whichacts on an optical isomer are introduced into the at least part of thehydroxy or amino groups except the hydroxy or amino groups modified withthe molecules of the compound represented by the general formula (I)through a urethane bond, a urea bond, an ester bond, or an ether bond.9. The complex according to claim 7, wherein the compound having afunctional group which acts on an optical isomer comprises a compoundcontaining an atomic group represented by the following general formula(VI) or (VII):[Chem 6]—CO—R′  (VI)—CO—NH—R′  (VII) where R′ represents an aliphatic or aromatichydrocarbon group which may contain a heteroatom, and the aliphatic oraromatic hydrocarbon group may be unsubstituted or may be substitutedwith one or more groups selected from the group consisting of ahydrocarbon group which has 1 to 12 carbon atoms and which may contain aheteroatom, a cyano group, a halogen, a hydroxy group, a nitro group, anamino group, and a dialkylamino group containing two alkyl groups eachhaving 1 to 8 carbon atoms.
 10. The complex according to claim 9,wherein the compound having a functional group which acts on an opticalisomer is 3,5-dimethylphenyl isocyanate.
 11. The complex according toclaim 1, wherein a content of the polymer compound derivative is 10 to90 wt % with respect to a total amount of the complex.
 12. The complexaccording to claim 1, wherein the compounds represented by the generalformula (II) comprise one or more compounds selected from the groupconsisting of tetraethoxysilane, tetramethoxysilane,tetra-n-propoxysilane, tetraisopropoxysilane, tetra-n-butoxysilane,tetraisobutoxysilane, tetra-sec-butoxysilane, tetra-t-butoxysilane,tetrapentyloxysilane, tetrahexyloxysilane, triethoxymethylsilane, andtriethoxyphenylsilane.
 13. The complex according to claim 1, wherein thecompounds represented by the general formula (V) comprise one or morecompounds selected from the group consisting ofbis(trimethoxysilyl)methane, bis(triethoxysilyl)methane,1,1-bis(trimethoxysilyl)ethane, 1,1-bis(triethoxysilyl)ethane,1,2-bis(trimethoxysilyl)ethane, 1,3-bis(trimethoxysilyl)propane,1,3-bis(triethoxysilyl)propane, 2,2-bis(trimethoxysilyl)propane,2,2-bis(triethoxysilyl)propane, 1,4-bis(trimethoxysilyl)benzene,1,4-bis(triethoxysilyl)benzene, and 1,2-bistriethoxysilylethane.
 14. Thecomplex according to claim 1, wherein the complex is in a bead form. 15.A method of producing a complex, the method comprising the steps of:dissolving a polymer compound derivative obtained by modifying part ofhydroxy or amino groups of a polymer compound having the hydroxy oramino groups with a compound represented by the following generalformula (I) and one or more kinds of compounds represented by thefollowing general formulae (II) to (V) in an organic solvent to preparea solution; and dropping the solution into an aqueous solution of asurfactant or a proton-donating solvent while stirring the aqueoussolution or the solvent:[Chem 7]A-X—Si(Y)_(n)R_(3-n)   (I) where A represents a reactive group whichreacts with a hydroxy or amino group, X represents an alkylene groupwhich has 1 to 18 carbon atoms and which may have a branch, or anarylene group which may have a substituent, Y represents a reactivegroup which reacts with a silanol group to form a siloxane bond, Rrepresents an alkyl group which has 1 to 18 carbon atoms and which mayhave a branch, or an aryl group which may have a substituent, and nrepresents an integer of 1 to 3.[Chem 8]M(OR¹)_(n)R² _(4-n)   (II)[Chem 9]Al(OR¹)_(p)R² _(3-p)   (III)[Chem 10]Mg(OR¹)_(q)R² _(2-q)   (IV) where M represents silicon (Si), titanium(Ti), zirconium (Zr), or chromium (Cr), Al represents aluminum, Mgrepresents magnesium, R¹ represents hydrogen or an alkyl group having 1to 12 carbon atoms, R² represents an alkyl group which has 1 to 18carbon atoms and which may have a branch or an aryl group which may havea substituent, n represents an integer of 1 to 4, p represents aninteger of 1 to 3, and q represents an integer of 1 or 2;[Chem 11][Si(OR³)_(n)R⁴ _(3-n)]—(X)—[Si(OR⁵)_(n)R⁶ _(3-n)]  (V) where R³, R⁴, R⁵,and R⁶ each independently represent an alkyl group which has 1 to 18carbon atoms and which may have a branch or an aryl group which may havea substituent, and X represents an alkylene group which has 1 to 18carbon atoms and which may have a branch or an arylene group which mayhave a substituent.
 16. A separating agent for optical isomers, theseparating agent comprising the complex according to claim 1.